Disease relevance of PDE6D

• The characterization of the canine PDE6D gene and its mapping provide important information for testing causal association of the gene with canine retinal degenerations, in particular rod-cone dysplasia 2 (rcd2) in collie dogs [1].
• The human gene (PDE6D) encoding a new subunit (delta) has been characterized and mapped to the long arm of chromosome 2 (HSA2q35-q36) where a new autosomal recessive retinitis pigmentosa (arRP) locus (RP26) has been localized [1].
• The property of p17 to increase production of proinflammatory cytokines could be a mechanism exploited by the virus to create a more suitable environment for HIV-1 infection and replication [2].
• We have reported that an antiserum prepared against thymosin alpha 1 [which shares a region of homology with the p17 protein of the acquired immunodeficiency syndrome (AIDS)-associated human immunodeficiency virus] effectively neutralized the AIDS virus and prevented its replication in H9 cells [3].
• From these studies, we conclude that the intracellular expression of a single-chain Ab to p17 inhibits HIV replication; in addition, the degree of inhibition is related to the intracellular targeting site [4].

High impact information on PDE6D

• GraB- induced caspase 3 processing to p17 in S-100 cytosol was increased only threefold in the presence of mitochondria, suggesting that another caspase(s) participates in the mitochondrial amplification of GraB apoptosis [5].
• Because HIV-1 infection and replication is related to cell activation and differentiation status, in the present study, we investigated the role played by p17 during the process of T cell stimulation [2].
• Upon induction of apoptosis, the large (p17) and small (p12) subunits, comprising active caspase-3, are generated via proteolytic processing of a latent proenzyme dimer [6].
• For example, a preponderance of natural sequence variants of the human immunodeficiency virus p17 Gag-derived peptide SLYNTVATL (SL9) are recognized by cytotoxic T lymphocytes, which implies that interactions with SL9 variants are degenerate both with respect to the class I MHC molecule and with respect to TCR [7].
• Furthermore, the caspase-3 p17 subunit, which has previously been shown to be S-nitrosylated and thereby inhibited, was denitrosylated by TNFalpha treatment suggesting that S-nitrosylation and denitrosylation are important regulatory mechanisms in endothelial cells contributing to the integrity of the endothelial cell monolayer [8].

Chemical compound and disease context of PDE6D

• METHODS: HIV-1 genotypes of 59 specimens were screened based on gag (p17) and env (C2/V3) regions [9].
• The search for mutations in NL4.3/SPL2923 in viral genes other than env revealed several mutations in the gene encoding the HIV p17 matrix protein (MA) and one mutation in the gene encoding the p24 capsid protein (CA) [10].

Biological context of PDE6D

• The human PDE delta gene (locus designation PDE6D) was localized to the long arm of chromosome 2 (2q35-q36) by fluorescence in situ hybridization [11].
• The human PDED gene consisted of 5 exons spanning at least 30 kb of genomic DNA [12].
• Canine PDE6D has been localized to canine radiation hybrid group 14-a, which extends conserved synteny between the dog, human chromosome 2q and mouse chromosome 1 [1].
• Transfection of cells with a p17 mutant, where the essential Cys-163 was mutated into alanine, completely prevented S-nitrosation of the enzyme [13].
• METHODS: Peripheral blood mononuclear cells (PBMC) obtained from healthy donors were cultured in the presence or absence of p17 with mitogens such as phytohaemagglutinin or interleukin-2 and their response assayed by cell proliferation [14].

Anatomical context of PDE6D

• A novel subunit, termed PDE delta (HGMW-approved symbol, PDE6D; MW 17 kDa), is able to detach PDE partially from bovine rod outer segment membranes under physiological conditions [11].
• Our data show that p17 exerts its biological activity after binding to a specific cellular receptor expressed on activated T lymphocytes [2].
• HIV p17 enhances lymphocyte proliferation and HIV-1 replication after binding to a human serum factor [14].
• BACKGROUND: Previously we reported that human CD4(+) T cell lines stably expressing anti-HIV-1 gag p17 scFv/Ckappa in the cytosol or nucleus were resistant to HIV-1 challenge [15].
• METHODS: Anti-HIV-1 gag p17 scFv/Ckappa gene that is targeted into cytoplasm was inserted into a MMLV vector and transfected into packaging cell line PT67 [15].

Associations of PDE6D with chemical compounds

• To demonstrate that the cysteine residue Cys-163 of caspase-3 is S-nitrosated, cells were transfected with the Myc-tagged p17 subunit of caspase-3 [13].
• Genetic subtyping based on gag (p17) and env (C2/V3) sequences revealed that CRF01_AE is a principal strain circulating throughout Vietnam, including the provinces near the China border [16].
• CRF01_AE was concluded to be a predominant strain and the nucleotide CSs in gag p17 and env-V3 showed only 1.26% and no difference from CS in the Los Alamos database, respectively [17].
• A Neospora caninum 17-19 kDa antigenic protein fraction (p17) in one-dimensional polyacrylamide gel electrophoresis (SDS-PAGE) is the immunodominant antigen recognized by sera from bovines naturally infected by N. caninum [18].

Other interactions of PDE6D

• A preliminary screen of all 5 exons in 20 unrelated patients with autosomal recessive retinitis pigmentosa revealed no PDED mutations [12].
• The P10 protein is a viroporin and induces cell fusion, whereas the biological function of P17 protein is completely unknown [19].

Analytical, diagnostic and therapeutic context of PDE6D

• Fluorescence in situ hybridisation (FISH) and radiation hybrid mapping localised the human PDED gene to chromosome 2q37 [12].
• The asymmetric unit contains a (p17/p12)2 tetramer, in agreement with the tetrameric structure of the protein in solution as determined by dynamic light scattering and size exclusion chromatography [20].
• METHODS: Sequences were generated from PCR products amplified directly (without cloning) from patient blood and compared in the v3/v4 region of env and the p17 and p24 regions of gag to reference subtype strains by phylogenetic analysis [21].
• CONCLUSIONS: The expression of the anti-HIV-1 gag p17 scFv/Ckappa gene construct in primary human T cells renders these cells resistant to HIV-1 and points to the potential clinical usefulness of this gene construct for anti-HIV-1 gene therapy [15].
• DESIGN: We performed a cross-sectional study of untreated HIV-1-infected subjects measuring HIV-1-specific interferon (IFN)-gamma-secreting CD4 T-cell responses against epitopes in Gag p17 and p24 and concurrent endogenous plasma HIV-1 RNA epitope sequence variation [22].

References